Abstract
MicroRNAs (miRNA) are small noncoding, single-stranded RNAs that inhibit gene expression at a posttranscriptional level, whose abnormal expression has been described in different tumors. The aim of our study was to identify miRNAs potentially implicated in chronic myeloid leukemia (CML). We detected an abnormal miRNA expression profile in mononuclear and CD34(+) cells from patients with CML compared with healthy controls. Of 157 miRNAs tested, hsa-miR-10a, hsa-miR-150, and hsa-miR-151 were down-regulated, whereas hsa-miR-96 was up-regulated in CML cells. Down-regulation of hsa-miR-10a was not dependent on BCR-ABL1 activity and contributed to the increased cell growth of CML cells. We identified the upstream stimulatory factor 2 (USF2) as a potential target of hsa-miR-10a and showed that overexpression of USF2 also increases cell growth. The clinical relevance of these findings was shown in a group of 85 newly diagnosed patients with CML in which expression of hsa-miR-10a was down-regulated in 71% of the patients, whereas expression of USF2 was up-regulated in 60% of the CML patients, with overexpression of USF2 being significantly associated with decreased expression of hsa-miR-10a (P = 0.004). Our results indicate that down-regulation of hsa-miR-10a may increase USF2 and contribute to the increase in cell proliferation of CML implicating a miRNA in the abnormal behavior of CML.
Highlights
MicroRNAs are noncoding, single-strandedRNAs of 21 to 25 nucleotides recently implicated in the regulation of several biological processes, such as cell cycle, apoptosis, differentiation, and development or tumorigenesis [1, 2]. miRNAs inhibit the expression of specific genes either by decreasing mRNA stability or by blocking mRNA translation [2,3,4,5]
We show that down-regulation of hsa-miR-10a results in increased expression of the upstream stimulatory factor 2 transcription factor (USF2), which contributes to the increased cell growth of chronic myeloid leukemia (CML) cells
Treatment of CML has notably been improved by the development of imatinib mesylate, a tyrosine kinase inhibitor that blocks the kinase activity of BCR-ABL1, defining this drug as the gold standard first-line therapy for CML patients [36, 40, 41]
Summary
MicroRNAs (miRNAs) are noncoding, single-strandedRNAs of 21 to 25 nucleotides recently implicated in the regulation of several biological processes, such as cell cycle, apoptosis, differentiation, and development or tumorigenesis [1, 2]. miRNAs inhibit the expression of specific genes either by decreasing mRNA stability or by blocking mRNA translation [2,3,4,5]. The first evidence for the involvement of miRNAs in human cancer was described in chronic lymphocytic leukemia in which deletion of a chromosomal region (13q14) was associated with down-regulation of miR-15a in the majority of chronic lymphocytic leukemia patients Abnormal expression of miRNAs has currently been described in numerous solid tumors, such as lung cancer [12, 13], breast cancer [14], glioblastoma [15], hepatocellular carcinoma [16], endocrine pancreatic tumors [17], papillary thyroid carcinoma [18], testicular germ cell tumors [19], and colorectal cancer [20, 21], and in hematologic malignancies, such as chronic lymphocytic leukemia [22], lymphomas [23], acute promyelocytic leukemia [24], and more recently acute lymphoblastic leukemia [25]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
